CCBE1 Is Essential for Epicardial Function during Myocardium Development

Funding: This work was supported by Fundação para a Ciência e a Tecnologia (FCT) grants (PTDC/MEC-CAR/29590/2017) to JA Belo and by the Scientific Employment Stimulus to JMI (Norma Transitória 8189/2018, FCT), and iNOVA4Health—UIDB/Multi/04462/2013, a program Int. J. Mol. Sci. 2022, 23, 12642 14 of 17 financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that promote myocardial growth. CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells that is required for the formation of the primitive coronary plexus. However, the role of CCBE1 during epicardial development was still unknown. Here, using a Ccbe1 knockout (KO) mouse model, we observed that loss of CCBE1 leads to congenital heart defects including thinner and hyper-trabeculated ventricular myocardium. In addition, Ccbe1 mutant hearts displayed reduced proliferation of cardiomyocyte and epicardial cells. Epicardial outgrowth culture assay to assess epicardial-derived cells (EPDC) migration showed reduced invasion of the collagen gel by EPDCs in Ccbe1 KO epicardial explants. Ccbe1 KO hearts also displayed fewer nonmyocyte/nonendothelial cells intramyocardially with a reduced proliferation rate. Additionally, RNA-seq data and experimental validation by qRT-PCR showed a marked deregulation of EMT-related genes in developing Ccbe1 mutant hearts. Together, these findings indicate that the myocardium defects in Ccbe1 KO mice arise from disruption of epicardial development and function.publishersversionpublishe

Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients

Fabry's disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detectGLAgene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence ofGLAgene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rareGLAvariant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No "classic" pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292).publishersversionpublishe

Influence of Match Status on Players’ Prominence and Teams’ Network Properties During 2018 FIFA World Cup

The analyses of players and teams’ behaviors during the FIFA World Cup may provide a better understanding on how football tactics and strategies have developed in the past few years in elite football. The Social Network Analysis (SNA) has been carried out in the investigations about passing distribution, improving the understanding on how players interact and cooperate during a match. In football official matches, studies have used the SNA as a means of coding players’ cooperation and opposition patterns. However, situational variables such as match status were previously investigated and associated with changes on teams’ dynamics within and/or between matches, but were not considered in studies based on Social Network Analysis. This study aimed to analyze the influence of match status on teams’ cooperation patterns and players’ prominence according to playing positions during 2018 FIFA World Cup. Fourteen matches of the knockout stage were analyzed. Macro and micro network measures were obtained from adjacency matrixes collected for each team, in each match status (winning, drawing, and losing). A one-way ANOVA was used to compare teams’ networks (macro-analysis variables) within each match status, while a two-way ANOVA (match status × playing position) was used to compare the micro-analysis variables. Results showed no differences between match status for macro analysis. Winning situations induced higher prominence in central midfielders (0.107; p = 0.001), wide midfielders (0.093; p = 0.001), and center forward (0.085; p = 0.001), while in losing situations lower prominence levels were observed for goalkeepers (0.044; p = 0.001) and center forward (0.074; p = 0.001). Data revealed that teams do not change macrostructures according to match status. On the other hand, the microstructures showed important adaptations regarding game styles, with changes in players’ behaviors according to playing positions. In general, the levels of centrality and prestige in players of different positions indicated a more direct play style in winning situations and a more build-up style in losing situations. These results allow a better understanding about the influence of match status on players’ and teams’ performance during high-level football competitions and may help coaches to improve athletes’ performance in these situations

Obstáculos no tratamento da dor pediátrica no Brasil: visão das crianças, uma parcial

Introdução: No Brasil, 40% dos servicos de Cuidados Paliativos Pediatricos ainda tem dificuldades ou nao tem acesso a opioides. Uma vez que o tratamento da dor na crianca e considerado essencial, devendo ser feito de maneira adequada e holistica, mas que atualmente esse cuidado ainda e negligenciado no ensino e na assistencia, os obstaculos devem ser elucidados para que haja avancos, sendo importante, a principio, elucidar de forma mais clara como a dor e entendida pela propria crianca. Objetivo: O objetivo deste trabalho e entender quais as barreiras para o tratamento da dor no Brasil na visao das criancas. Método: Estudo observacional, exploratorio-descritivo e transversal, aprovado pelo Comite de Etica em Pesquisa da instituicao em questao, com inicio da coleta de dados em maio de 2022. Foram convidadas para participar da pesquisa criancas de 8 a 18 anos de idade, internadas nas enfermarias de um Hospital Universitario vinculado a uma universidade federal, fora do periodo de instabilidade clinica. Apos a concordancia em participar da pesquisa, assim como assinatura do Termo de Consentimento Livre e Esclarecido pelo responsavel e Termo de Assentimento Livre e Esclarecido pelo entrevistado, foram realizadas entrevistas presenciais, com roteiro de perguntas tendo apoio em outros estudos ja publicados e encontrados por revisao de literatura sobre dor em pediatria. Resultados: Foram entrevistadas 8 criancas, de 8 a 16 anos de idade, sendo 5 do sexo feminino, 2 do masculino e 1 que preferiu nao dizer. Apenas 1 dos pesquisados disse que nao se preocupava com a dor que poderia sentir em seu tratamento, sendo que 2 relataram que tem dificuldades em auto-reconhecer quando estao com dor. Todos acharam importante o profissional de saude saber tratar dor em pediatria. Um dado importante que ser apontado e que 50% dos participantes relataram que ja tiveram muitas dores que seus pais ou a equipe de saude disseram que nao era nada e ficaram tristes por isso. Conclusão: Ainda ha obstaculos importantes para que a dor pediatrica no Brasil seja adequadamente avaliada e tratada, sendo que mais pesquisas na area devem ser feitas, assim como acoes educativas para profissionais de saude e populacao em geral tambem.info:eu-repo/semantics/publishedVersio

Results from the portuguese register

Objective Our aims were to evaluate the correlation between Juvenile Arthritis Disease Activity Score 27-joint reduced count (JADAS27) with erythrocyte sedimentation rate (ESR) and JADAS27 with C-reactive protein (CRP) scores and to test the agreement of both scores on classifying each disease activity state. We also aimed at verifying the correlation of the 2 scores across juvenile idiopathic arthritis (JIA) categories and to check the correlation between JADAS27-ESR and clinical JADAS27 (JADAS27 without ESR). Methods A nationwide cohort of patients with JIA registered in the Portuguese Register, Reuma.pt, was studied. JADAS27-CRP was adapted by replacing ESR with CRP level as the inflammatory marker. JADAS27-CRP was calculated similarly to JADAS27-ESR as the simple linear sum of its 4 components. Pearson's correlations and K statistics were used in the analyses. Results A total of 358 children had full data to calculate JADAS27; 65.4% were female and the mean ± SD disease duration was 11.8 ± 9.1 years. The correlation coefficient between JADAS27-ESR and JADAS27-CRP was 0.967 (P < 0.0001), although the correlation coefficient between ESR and CRP level was 0.335 (P < 0.0001). The strong correlation between JADAS27-ESR and JADAS27-CRP was maintained when compared within each JIA category. The agreement between JADAS27-ESR and JADAS27-CRP across the 4 activity states was very good, showing 91.1% of the observations in agreement; K = 0.867 (95% confidence interval 0.824-0.91). The correlation between JADAS27 with ESR and JADAS27 without ESR was high (r = 0.97, P < 0.0001). Conclusion JADAS27 based on CRP level correlated closely with JADAS27-ESR across all disease activity states and JIA categories, indicating that both measures can be used in clinical practice. Moreover, the correlation of JADAS27 with and without ESR was also high, suggesting that this tool might be useful even in the absence of laboratorial measures.publishersversionpublishe

Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt

Methods. We prospectively collected patient and disease characteristics from patients with JIA who started biological therapy. Adverse events were collected during the follow-up period. Predictors of response at 1 year and drug retention rates were assessed at 4 years of treatment for the first biologic agent.Results. A total of 812 JIA patients [65% females, mean age at JIA onset 6.9 years (s.d. 4.7)], 227 received biologic therapy; 205 patients (90.3%) were treated with an anti-TNF as the first biologic. All the parameters used to evaluate disease activity, namely number of active joints, ESR and Childhood HAQ/HAQ, decreased significantly at 6 months and 1 year of treatment. The mean reduction in Juvenile Disease Activity Score 10 (JADAS10) after 1 year of treatment was 10.4 (s.d. 7.4). According to the definition of improvement using the JADAS10 score, 83.3% respond to biologic therapy after 1 year. Fourteen patients discontinued biologic therapies due to adverse events. Retention rates were 92.9% at 1 year, 85.5% at 2 years, 78.4% at 3 years and 68.1% at 4 years of treatment. Among all JIA subtypes, only concomitant therapy with corticosteroids was found to be univariately associated with withdrawal of biologic treatment (P = 0.016).Conclusion. Biologic therapies seem effective and safe in patients with JIA. In addition, the retention rates for the first biologic agent are high throughout 4 years

Defensive interactions in soccer small-sided games: an integrated approach between the fundamental tactical principles and the social network analysis

This study aimed to 1) present a new analysis of the interactions between the tactical principles of defensive coverage and delay using the Social Network Analysis (SNA); 2) compare the defensive cooperation patterns presented by players of different categories during a 3vs.3 soccer small-sided games SSG; 3) compare the level of defensive prominence presented by defenders, midfielders, and forwards in 3vs.3 SSG within and between different categories. Twenty-eight soccer athletes from U-13 (n=14) and U-14 (n=14) categories of a sports club performed 3vs.3 SSG for the analysis of the defensive tactical principles. Defensive interactions were considered successful defensive coverage and a delay actions performed within the same time interval. Macro (density and clustering coefficient) and micro (degree centrality, degree prestige and page rank) analyses were used as SNA measures. Results indicated no significant differences between categories for the macro and micro analyses. Only in the U-14 category, midfielders presented higher prominence levels than the other playing positions (p=0.004). We concluded that U-13 and U-14 athletes are not different regarding defensive cooperation patterns. A higher positional tactical knowledge obtained through deliberate practice is essential to induce different defensive interactions between playing positions, as shown by significant differences only in the U-14 category

Use of physical activity and cardiorespiratory fitness in identifying cardiovascular risk factors in male brazilian adolescents

The aim of this study was to investigate the impact of physical activity (PA) and cardiorespiratory fitness (CRF) levels on the prevalence of overweight and high blood pressure levels in adolescents. In this observational, cross-sectional study, 614 boys aged 10-14 years were assessed for height, body mass, body mass index (BMI), waist circumference (WC) and blood pressure (BP). CRF was assessed using a run test (Léger Test) and subjects were then grouped according to their CRF level. PA level was assessed through a questionnaire (The Three Day Physical Activity Recall) and classified into two groups, namely > 300 minutes of PA/week and < 300 minutes of PA/week. Maturational stage was evaluated according to the development of pubic hair (self-assessment) as proposed by Tanner. We used statistical descriptive analysis, univariate and multivariate analyses in the total participants and subjects were divided by age. Fifty percent of the sample performed < 300 minutes of PA/week and 67.6% had unsatisfactory CRF levels. There was a higher prevalence of unsatisfactory CRF levels among subjects with altered BMI (overweight), WC (abdominal obesity) or BP (high blood pressure) for all age groups. PA history, however, did not show any significance. A total of 31% of participants were overweight, 24.8% had abdominal obesity and 15.4% had increased BP. Unsatisfactory CRF levels were found to be a better predictor for the diagnosis of cardiovascular diseases (CV) risk factors than PA history, regardless of age group

Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Santiago, Chile: a cluster randomized controlled trial. a study protocol [ISRCTN 02694183]

BACKGROUND: Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. Less is known about subclinical vitamin B12 deficiency and concurrent neuroconduction and cognitive impairment. A Programme of Complementary Feeding for the Older Population (PACAM) in Chile delivers 2 complementary fortified foods that provide approximately 1.4 μg/day of vitamin B12 (2.4 μg/day elderly RDA). The aim of the present study is to assess whether supplementation with vitamin B12 will improve neuroconduction and cognitive function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of clinical deficiency. METHODS: We designed a cluster double-blind placebo-controlled trial involving community dwelling people aged 70-79 living in Santiago, Chile. We randomized 15 clusters (health centers) involving 300 people (20 per cluster). Each cluster will be randomly assigned to one of three arms: a) a 1 mg vitamin B12 pill taken daily and a routine PACAM food; b) a placebo pill and the milk-PACAM food fortified to provide 1 mg of vitamin B12; c) the routine PACAM food and a placebo pill.The study has been designed as an 18 month follow up period. The primary outcomes assessed at baseline, 4, 9 and 18 months will be: serum levels of vitamin B12, neuroconduction and cognitive function. CONCLUSIONS: In view of the high prevalence of vitamin B12 deficiency in later life, the present study has potential public health interest because since it will measure the impact of the existing program of complementary feeding as compared to two options that provide higher vitamin B12 intakes that might potentially may contribute in preserving neurophysiologic and cognitive function and thus improve quality of life for older people in Chile. TRIAL REGISTRATION: ISRCTN: ISRCTN02694183

Adoption and patterns of use of invasive physiological assessment of coronary artery disease in a large cohort of 40 821 real-world procedures over a 12-year period

Funding Information: The authors wish to acknowledge the invaluable contributions of Paulo Leal regarding data acquisition and management, and John Henderson for statistical consultancy. Publisher Copyright: © 2021 Sociedade Portuguesa de CardiologiaIntroduction and Objectives: Use of invasive physiological assessment in patients with coronary artery disease varies widely and is perceived to be low. We aimed to examine adoption rates as well as patterns and determinants of use in an unselected population undergoing invasive coronary angiography over a long time frame. Methods: We retrospectively determined the per-procedure prevalence of physiological assessment in 40 821 coronary cases performed between 2007 and 2018 in two large-volume centers. Adoption was examined according to procedure type and patient- and operator-related variables. Its association with relevant scientific landmarks, such as the release of clinical trial results and practice guidelines, was also assessed. Results: Overall adoption was low, ranging from 0.6% in patients undergoing invasive coronary angiography due to underlying valve disease, to 6% in the setting of stable coronary artery disease (CAD); it was 3.1% in patients sustaining an acute coronary syndrome. Of scientific landmarks, FAME 1, the long-term results of FAME 2 and the 2014 European myocardial revascularization guidelines were associated with changes in practice. Publication of instantaneous wave-free ratio (iFR) trials had no influence on adoption rates, except for a higher proportion of iFR use. In 42.9% of stable CAD patients undergoing percutaneous coronary intervention there was no objective non-invasive evidence of ischemia, nor was physiological assessment performed. Younger operator age (4.5% vs. 4.0% vs. 0.9% for ages 55 years, respectively; p<0.001) and later time of procedure during the day (2.9% between 6 and 8 p.m. vs. 4.4% at other times) were independent correlates of use of invasive physiology. Conclusions: Our study confirms the low use of invasive physiology in routine practice. The availability of resting indices did not increase adoption. Strategies are warranted to promote guideline implementation and to improve patient care and clinical outcomes.publishersversionpublishe